Adenylyl cyclases are important mediators of signaling through G protein-coupled receptors. Adenylyl cyclase type 1 (AC1) belongs to a family of adenylyl cyclases that are stimulated by calcium in a calmodulin-dependent manner. Notably, AC1 is associated with chronic pain responses in several regions of the central nervous system. Accordingly, inhibition of AC1 has resulted in analgesic effects in both neuroinflammatory and neuropathic pain in rodent models. A dearth of AC1 inhibiting compounds and an inability to efficiently synthesize them means that their analgesic benefits cannot be widely realized and people continue to suffer from neuropathic and inflammatory pain.